Primary ciliary dyskinesia 29

Summary

Primary ciliary dyskinesia 29 (MONDO:0014378) is a disease caused by CCNO (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: CCNO (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 29
Mondo ID	MONDO:0014378
OMIM	615872
DOID	DOID:0110600
NCIT	C172393
UMLS	C4014534
MedGen	862971
GARD	0016025
Is cancer (heuristic)	no

Also known as: CCNO primary ciliary dyskinesia · CILD29 · ciliary dyskinesia, primary, 29 · ciliary dyskinesia, primary, type 29 · primary ciliary dyskinesia caused by mutation in CCNO · primary ciliary dyskinesia type 29

Data availability: 30 ClinVar variants · 3 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 29

Related subtypes (58): ciliary discoordination due to random ciliary orientation, ciliary dyskinesia with transposition of ciliary microtubules, ciliary dyskinesia with defective radial spokes, ciliary dyskinesia with excessively long cilia, Stromme syndrome, primary ciliary dyskinesia 1, ciliary dyskinesia, primary, 36, X-linked, primary ciliary dyskinesia 2, primary ciliary dyskinesia 3, primary ciliary dyskinesia 4, primary ciliary dyskinesia 5, primary ciliary dyskinesia 6, primary ciliary dyskinesia 7, primary ciliary dyskinesia 8, primary ciliary dyskinesia 9, primary ciliary dyskinesia 10, primary ciliary dyskinesia 11, primary ciliary dyskinesia 12, primary ciliary dyskinesia 13, primary ciliary dyskinesia 14, primary ciliary dyskinesia 15, primary ciliary dyskinesia 16, primary ciliary dyskinesia 17, primary ciliary dyskinesia 18, primary ciliary dyskinesia 19, primary ciliary dyskinesia 20, primary ciliary dyskinesia 21, primary ciliary dyskinesia 22, primary ciliary dyskinesia 23, primary ciliary dyskinesia 24, primary ciliary dyskinesia 25, primary ciliary dyskinesia 26, primary ciliary dyskinesia 27, primary ciliary dyskinesia 28, primary ciliary dyskinesia 30, primary ciliary dyskinesia 32, primary ciliary dyskinesia 33, primary ciliary dyskinesia 34, primary ciliary dyskinesia 35, ciliary dyskinesia, primary, 46, ciliary dyskinesia, primary, 47, and lissencephaly, ciliary dyskinesia, primary, 48, without situs inversus, ciliary dyskinesia, primary, 39, ciliary dyskinesia, primary, 40, ciliary dyskinesia, primary, 41, ciliary dyskinesia, primary, 42, ciliary dyskinesia, primary, 43, ciliary dyskinesia, primary, 44, ciliary dyskinesia, primary, 45, ciliary dyskinesia, primary, 37, ciliary dyskinesia, primary, 38, ciliary dyskinesia, primary, 54, ciliary dyskinesia, primary, 49, without situs inversus, ciliary dyskinesia, primary, 50, ciliary dyskinesia, primary, 51, ciliary dyskinesia, primary, 52, ciliary dyskinesia, primary, 53, CFAP46-related primary ciliary dyskinesia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

30 retrieved; paginated sample, class counts are floors:

10 pathogenic, 9 uncertain significance, 7 likely pathogenic, 2 pathogenic/likely pathogenic, 1 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333420	NM_021147.5(CCNO):c.906del (p.Leu303fs)	CCNO	Pathogenic	criteria provided, single submitter
139599	NM_021147.5(CCNO):c.248_252dup (p.Gly85fs)	CCNO	Pathogenic	criteria provided, multiple submitters, no conflicts
139600	NM_021147.5(CCNO):c.258_262dup (p.Gln88fs)	CCNO	Pathogenic	criteria provided, multiple submitters, no conflicts
139601	NM_021147.5(CCNO):c.926del (p.Pro309fs)	CCNO	Pathogenic	no assertion criteria provided
139603	NM_021147.5(CCNO):c.263_267dup (p.Val90fs)	CCNO	Pathogenic	criteria provided, multiple submitters, no conflicts
139611	NM_021147.5(CCNO):c.481_482del (p.Leu161fs)	CCNO	Pathogenic	criteria provided, single submitter
1453435	NM_021147.5(CCNO):c.307C>T (p.Gln103Ter)	CCNO	Pathogenic	criteria provided, multiple submitters, no conflicts
4755437	NM_021147.5(CCNO):c.379C>T (p.Gln127Ter)	CCNO	Pathogenic	criteria provided, single submitter
665170	NM_021147.5(CCNO):c.259_268dup (p.Val90fs)	CCNO	Pathogenic	criteria provided, multiple submitters, no conflicts
800814	NM_021147.5(CCNO):c.425del (p.Pro142fs)	CCNO	Pathogenic	criteria provided, single submitter
951909	NM_021147.5(CCNO):c.427dup (p.Val143fs)	CCNO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2085	NM_000159.4(GCDH):c.1204C>T (p.Arg402Trp)	GCDH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
139602	NM_021147.5(CCNO):c.961C>T (p.Gln321Ter)	CCNO	Likely pathogenic	criteria provided, single submitter
2441875	NM_021147.5(CCNO):c.564_567+1delinsTCATCGCTTGCATCGCTTGCATCGCTTGCATCGC	CCNO	Likely pathogenic	criteria provided, single submitter
2502875	NM_021147.5(CCNO):c.548T>A (p.Leu183Ter)	CCNO	Likely pathogenic	criteria provided, single submitter
4755423	NM_021147.5(CCNO):c.12_13del (p.Cys5fs)	CCNO	Likely pathogenic	criteria provided, single submitter
4846983	NM_021147.5(CCNO):c.909del (p.Leu303fs)	CCNO	Likely pathogenic	criteria provided, single submitter
812691	NM_021147.5(CCNO):c.964del (p.Leu322fs)	CCNO	Likely pathogenic	no assertion criteria provided
2664880	NM_016343.4(CENPF):c.8124_8127delinsAGC (p.Lys2709fs)	CENPF	Likely pathogenic	criteria provided, single submitter
416791	NM_021147.5(CCNO):c.134C>A (p.Pro45His)	CCNO	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032118	NM_021147.5(CCNO):c.368C>T (p.Ala123Val)	CCNO	Uncertain significance	criteria provided, single submitter
1698884	NM_021147.5(CCNO):c.265C>G (p.Pro89Ala)	CCNO	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582358	NM_021147.5(CCNO):c.714_715delinsTG (p.Glu238_His239delinsAspAsp)	CCNO	Uncertain significance	criteria provided, single submitter
3065022	NM_021147.5(CCNO):c.715C>G (p.His239Asp)	CCNO	Uncertain significance	criteria provided, single submitter
3902048	NM_021147.5(CCNO):c.381+10T>G	CCNO	Uncertain significance	criteria provided, single submitter
411593	NM_021147.5(CCNO):c.491T>C (p.Phe164Ser)	CCNO	Uncertain significance	criteria provided, multiple submitters, no conflicts
4292645	NM_021147.5(CCNO):c.556G>A (p.Ala186Thr)	CCNO	Uncertain significance	criteria provided, single submitter
4533363	NM_021147.5(CCNO):c.381+5G>A	CCNO	Uncertain significance	criteria provided, single submitter
648428	NM_021147.5(CCNO):c.187T>C (p.Ser63Pro)	CCNO	Uncertain significance	criteria provided, multiple submitters, no conflicts
416790	NM_021147.5(CCNO):c.957G>A (p.Lys319=)	CCNO	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CCNO	Definitive	Autosomal recessive	primary ciliary dyskinesia 29	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCNO	Orphanet:244	Primary ciliary dyskinesia
CENPF	Orphanet:444069	Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
CENPF	Orphanet:506307	Stromme syndrome
GCDH	Orphanet:25	Glutaryl-CoA dehydrogenase deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCNO	HGNC:18576	ENSG00000152669	P22674	Cyclin-O	gencc,clinvar
CENPF	HGNC:1857	ENSG00000117724	P49454	Centromere protein F	clinvar
GCDH	HGNC:4189	ENSG00000105607	Q92947	Glutaryl-CoA dehydrogenase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCNO	Cyclin-O	Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation.
CENPF	Centromere protein F	Required for kinetochore function and chromosome segregation in mitosis.
GCDH	Glutaryl-CoA dehydrogenase, mitochondrial	Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCNO	Enzyme (other)	yes	3.2.2.27	Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CENPF	Other/Unknown	no		CenpF/LEK1_Rb-prot-bd, Centromere_CenpF_N, Centromere_CenpF_leu-rich_rpt
GCDH	Enzyme (other)	yes	1.3.8.6	Acyl-CoA_DH_CS, AcylCoA_DH/ox_M, AcylCo_DH/oxidase_C

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of bronchus	1
oocyte	1
secondary oocyte	1
embryo	1
ganglionic eminence	1
ventricular zone	1
apex of heart	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCNO	172	broad	marker	oocyte, secondary oocyte, epithelium of bronchus
CENPF	207	ubiquitous	marker	ventricular zone, ganglionic eminence, embryo
GCDH	259	ubiquitous	marker	right lobe of liver, liver, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CENPF	2,876
GCDH	2,573
CCNO	1,859

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GCDH	Q92947	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCNO	P22674	79.06
CENPF	P49454

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Lysine catabolism	1	571.0×	0.035	GCDH
Polo-like kinase mediated events	1	317.2×	0.035	CENPF
Amplification of signal from the kinetochores	1	98.5×	0.041	CENPF
Mitotic Spindle Checkpoint	1	79.3×	0.041	CENPF
Mitotic G2-G2/M phases	1	63.4×	0.041	CENPF
G2/M Transition	1	63.4×	0.041	CENPF
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	58.3×	0.041	CENPF
Mitotic Metaphase and Anaphase	1	48.4×	0.041	CENPF
Mitotic Anaphase	1	48.4×	0.041	CENPF
EML4 and NUDC in mitotic spindle formation	1	46.4×	0.041	CENPF
Cell Cycle Checkpoints	1	44.3×	0.041	CENPF
Resolution of Sister Chromatid Cohesion	1	43.3×	0.041	CENPF
RHO GTPases Activate Formins	1	38.8×	0.041	CENPF
Mitotic Prometaphase	1	34.6×	0.041	CENPF
RHO GTPase Effectors	1	34.0×	0.041	CENPF
M Phase	1	33.0×	0.041	CENPF
Separation of Sister Chromatids	1	30.4×	0.042	CENPF
Cell Cycle, Mitotic	1	24.1×	0.050	CENPF
Cell Cycle	1	18.0×	0.062	CENPF
Signaling by Rho GTPases	1	17.1×	0.062	CENPF
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.062	CENPF
Signal Transduction	1	5.1×	0.187	CENPF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitotic cell cycle	2	89.2×	0.004	CCNO, CENPF
obsolete L-tryptophan metabolic process	1	1872.4×	0.007	GCDH
regulation of striated muscle tissue development	1	936.2×	0.007	CENPF
multi-ciliated epithelial cell differentiation	1	936.2×	0.007	CCNO
fatty-acyl-CoA biosynthetic process	1	624.1×	0.007	GCDH
cell division	2	30.8×	0.007	CCNO, CENPF
fatty acid beta-oxidation using acyl-CoA dehydrogenase	1	468.1×	0.007	GCDH
regulation of G2/M transition of mitotic cell cycle	1	432.1×	0.007	CENPF
kinetochore assembly	1	401.2×	0.007	CENPF
metaphase chromosome alignment	1	351.1×	0.007	CENPF
ventricular system development	1	280.9×	0.008	CENPF
DNA biosynthetic process	1	267.5×	0.008	CENPF
seminiferous tubule development	1	255.3×	0.008	CCNO
mitotic spindle assembly checkpoint signaling	1	187.2×	0.010	CENPF
G1/S transition of mitotic cell cycle	1	66.9×	0.025	CCNO
single fertilization	1	61.1×	0.025	CCNO
chromosome segregation	1	57.9×	0.025	CENPF
muscle organ development	1	55.6×	0.025	CENPF
kidney development	1	46.8×	0.028	CENPF
cilium assembly	1	24.5×	0.050	CCNO
response to xenobiotic stimulus	1	23.0×	0.051	CENPF
protein transport	1	14.6×	0.076	CENPF
spermatogenesis	1	11.7×	0.090	CCNO
negative regulation of DNA-templated transcription	1	10.5×	0.096	CENPF
cell differentiation	1	9.7×	0.100	CENPF

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GCDH	BALSALAZIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GCDH	1	4
CCNO	0	0
CENPF	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BALSALAZIDE	4	GCDH

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CCNO	22	Binding:22
GCDH	15	Binding:14, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CCNO	3.2.2.27	uracil-DNA glycosylase
GCDH	1.3.8.6	glutaryl-CoA dehydrogenase (ETF)

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
BALSALAZIDE	4	GCDH

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GCDH
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CCNO
E	Difficult family or no structure, no drug	1	CENPF

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CCNO	22	—
CENPF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.